Our studies are being directed toward a complete understanding of the cells involved in the induction of IgA responses. Our results, as well as those of others, have demonstrated the existence of a common mucosal immune system in which ingested antigens sensitize lymphoid cells in gut-associated lymphoid tissue (GALT) and subsequently result in IgA responses in secretory tissues including salivary and mammary glands. Recent studies from this laboratory have shown that lipopolysaccharide (LPS) from the indigenous Gram negative gut microflora influences the inductive events of antigen stimulation of Galt in an LPS responsive host. Specifically, LPS affects T lymphocytes in GALT which suppress GALT responses to T dependent antigen and ultimately results in oral tolerance. LPS nonresponsive C3H/HeJ mice do not harbor this population of LPS-induced T suppressor cell population and thus manifest elevated IgA responses to T dependent antigens. Oral tolerance is not induced in this mouse strain with prolonged oral administration of antigen. Furthermore, oral administration of S. mutans antigen to C3H/HeJ mice results in higher IgA immune than are seen in similarly-treated, LPS responsive C3H/HeN mice. These results suggest an important role for T cells in the induction of IgA immune responses to S. mutans antigens. The availability of unique animal models will allow evaluation of the most effective dose and form of antigen which will lead to optimal IgA responses in external secretions.